An ANR-funded postdoctoral positions (2 years with possibility of a 3rd year) is available in January 2023 within Dr. Damien Arnoult’s laboratory at INSERM U1197 based in Paul Brousse hospital in Villejuif. We are investigating the mitochondrial stress and the mitonuclear communications. Mitochondria are organelles that form the core of energy metabolism but they are also involved in the regulation of intermediate metabolism, apoptosis, innate immunity, and calcium buffering. Defects in mitochondrial proteins and/or mitochondrial dysfunction affecting muscular, metabolic, neurological, and the immune system are responsible of many human pathologies. Therefore, cells must rapidly adapt to environmental stresses that affect mitochondrial function. Accordingly, different forms of mitonuclear communication are involved in the synchronized modifications in the expression of proteins encoded by both the mitochondrial and nuclear genomes in response to various stressors or to preserve basal homeostasis. Recently, an OMA1-DELE1-HRI axis has been reported to be involved in the initiation of an Integrated Stress Response (ISR) after a mitochondrial stress, to allow the expression of specific cytoprotective genes that reprogram and renew cellular metabolism toward the synthesis of key metabolites. However, this OMA1-DELE1-HRI axis has only been explored in transformed cultured cells that mainly use glycolysis rather than mitochondria to produce energy in contrast to tissues such as muscles where energy production largely depends on mitochondria. There is thus a pressing need to explore the physiological role of this OMA1-DELE1- HRI axis in the mitochondria-mediated ISR in vivo, notably in muscle, and to better characterize its specific modes of regulation and activation.
Tagged as: Life Sciences
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